ADP-ribosylation factor-binding protein GGA1; gamma-adaptin-related protein 1; Golgi-localized, gamma ear-containing, ARF-binding protein 1 (GGA1)

Function: - plays a role in protein sorting & trafficking between trans-Golgi network (TGN) & endosomes - mediates ARF-dependent recruitment of clathrin to the TGN & binds ubiquitinated proteins & membrane cargo molecules with a cytosolic acidic cluster-dileucine (AC-LL) motif - phosphorylated by CK2 & dephosphorylated by PP2A - phosphorylation of GGA1 allows the internal AC-LL motif to bind the VHS domain & to inhibit recognition of cargo signals - phosphorylated upon DNA damage, probably by ATM or ATR - ubiquitinated (putative) - interacts with NECAP1 - interacts with CNST - interacts with GGA2 & GGA3 - binds to clathrin & activated ARFs - interacts with RABEP1 & RABGEF1 - interacts with type-1 membrane proteins SORT1, SORL1, LRP3, M6PR/CD-MPR, IGF2R/CI-MPR & BACE1 - binds CCDC91, P200, SYNRG, EPN4, NECAP2 & AFTPH/aftiphilin - interacts with TSG101 & UBC Structure: - monomer - the VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by 2 Leu (AC-LL motif) - the GAT domain a) is responsible for interaction with ARF-GTP, UBC & RABEP1 b) is required for recruitment to the TGN c) prevents ARF-GTP hydrolysis - the unstructured hinge region contains clathrin-binding but no autoinhibitory (AC-LL) motifs - the GAE domain binds accessory proteins regulating GGAs function - belongs to the GGA protein family - contains 1 GAE domain - contains 1 GAT domain - contains 1 VHS domain Compartment: - Golgi, trans-Golgi network - membrane; peripheral membrane, endosome membrane Alternative splicing: named isoforms=2 Expression: ubiquitously expressed Note: - uncertain whether Met-1 or Met-5 is the initiator

Properties

SIZE: entity length = 639 aa MW = 70 kD COMPARTMENT: golgi MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl VHS domain {17-147} ARF3 interaction {114-274} GAT {171-299} MOTIF: Ser phosphorylation site {S236} Unstructured hinge {300-509} MOTIF: Ser phosphorylation site {S355} Autoinhibitory {358-362} GAE {510-631}

Database Correlations

OMIM 606004 UniProt Q9UJY5 PFAM correlations Entrez Gene 26088 Kegg hsa:26088

References

UniProt :accession Q9UJY5